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01-08-2019 | Melanoma | Original Article

Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade

Authors: Jun Zhou, Jingjing Li, Indira Guleria, Tianqi Chen, Anita Giobbie-Hurder, Jonathan Stevens, Meghna Gupta, Xinqi Wu, Ryan C. Brennick, Michael P. Manos, F. Stephen Hodi

Published in: Cancer Immunology, Immunotherapy | Issue 8/2019

Abstract

Expression of inhibitors of apoptosis protein (IAP) family members is associated with poor prognosis in cancer patients. Immunity to ML-IAP (livin) and survivin has been well studied in patients with a variety of tumors. XIAP, the most potent inhibitor of apoptosis, is widely expressed in melanoma. To better define its potential role as an immunogenic target, cellular and humoral responses to XIAP were investigated in patients with advanced melanoma. An overlapping peptide library covering the full length of the XIAP protein was used to screen T cell responses of peripheral blood mononuclear cells (PBMC) from stage-IV melanoma patients treated with or without anti-CTLA4 (ipilimumab). The screen identified an array of peptides that predominantly induced CD4⁺ T cell responses. XIAP epitope-specific CD4⁺ T cells revealed proliferative responses to melanoma cells that express XIAP. Humoral responses to XIAP were also explored. Cellular and humoral responses to XIAP were associated with beneficial clinical outcomes after ipilimumab-based treatment, supporting XIAP as a potential therapeutic target.

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Title: Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade
Authors: Jun Zhou
Jingjing Li
Indira Guleria
Tianqi Chen
Anita Giobbie-Hurder
Jonathan Stevens
Meghna Gupta
Xinqi Wu
Ryan C. Brennick
Michael P. Manos
F. Stephen Hodi
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Melanoma
Melanoma
Published in: Cancer Immunology, Immunotherapy / Issue 8/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02370-4

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